A Phase I Study Using Submyeloablative DOsing of Intravenous Busulfan (Busulfex) for Refractory Brain Tumors
Pediatric brain tumors remain among the most common malignancies in childhood, second only
to leukemia, representing 20% of all childhood cancers in the United States (1). Although
significant strides have been made in therapies for other pediatric malignancies, mortality
for patients with brain tumors remains high. The mainstay of therapy for CNS tumors has been
a combination of surgery, chemotherapy, and radiation. High dose chemotherapy with stem
cell transplant has been proposed as an alternative to radiation, in very young children and
for relapsed patients. Stem cell transplantation however is not without significant side
effects as well as transplant related mortality.
Busulfan is an alkylating agent and is able to exert its cytotoxic effects through
hydrolysis and subsequent production of carbonium ions, directly alkylating DNA, interfering
with its replication, and ultimately leading to cell death (2). Busulfan readily crosses
the blood barrier, allowing for CNS levels nearly equal to those of plasma levels (5,6).
Primary Objectives:
To determine the maximum tolerated dose (MTD) of Busulfex ® in children with recurrent,
progressive, or refractory primary brain tumors.
Secondary Objectives:
To obtain preliminary data regarding progression free survival (PFS) and event free survival
(EFS) when Busulfex ® is used at submyeloablative doses in children with recurrent,
progressive, or refractory primary brain tumors.
To describe the plasma pharmacokinetics of Busulfex ® in children with recurrent,
progressive, or refractory primary brain tumors, using a continuous infusion.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
maximum tolerated dose (MTD)
2 years
Yes
Stewart Goldman, MD
Principal Investigator
Ann & Robert H Lurie Children's Hospital of Chicago
United States: Food and Drug Administration
CNS 1100
NCT00836628
Name | Location |
---|---|
Children's Memorial Hospital | Chicago, Illinois 60614 |